Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.
Biochem Biophys Res Commun. 2021 Aug 20;566:36-44. doi: 10.1016/j.bbrc.2021.05.097. Epub 2021 Jun 8.
The number of patients with non-alcoholic steatohepatitis (NASH) and inflammatory bowel disease (IBD) is increasing. This study elucidates the effect of both NASH and IBD on hepatocellular carcinoma (HCC) using a mouse model combining NASH and IBD. The melanocortin 4 receptor-deficient (Mc4r-KO) mice were divided into four groups with or without a high-fat diet (HFD) and with or without dextran sulfate sodium (DSS) to induce colitis, and the differences in liver damage and occurrence of HCC were analyzed. In the HFD + DSS group, the body weight, liver weight/body weight ratio, and serum levels of albumin and alanine aminotransferase were significantly lower than those in the HFD group. We further found that steatosis was significantly lower and lobular inflammation was significantly higher in the HFD + DSS group than those in the HFD group, and that individual steatosis and lobular inflammation state in the HFD + DSS mice varied. We detected HCC only in the HFD + DSS group, and mice with severe steatosis and mild colitis were found to be at high risk of HCC. Presently, the prediction of HCC is very difficult. In some cases, severe colitis reverses the fat accumulation due to appetite loss. Our findings clearly showed that severe steatohepatitis and mild colitis are simultaneously essential for the occurrence of HCC in patients with NASH and IBD.
非酒精性脂肪性肝炎（NASH）和炎症性肠病（IBD）患者的数量正在增加。本研究通过建立合并 NASH 和 IBD 的小鼠模型，阐明了 NASH 和 IBD 对肝细胞癌（HCC）的影响。将黑皮质素 4 受体缺陷（Mc4r-KO）小鼠分为四组，分别给予高脂肪饮食（HFD）和/或葡聚糖硫酸钠（DSS）以诱导结肠炎，并分析肝脏损伤和 HCC 发生的差异。在 HFD+DSS 组，体重、肝重/体重比以及血清白蛋白和丙氨酸氨基转移酶水平明显低于 HFD 组。我们进一步发现，与 HFD 组相比，HFD+DSS 组的脂肪变性明显减轻，肝小叶炎症明显加重，且 HFD+DSS 小鼠的单个脂肪变性和肝小叶炎症状态存在差异。我们仅在 HFD+DSS 组检测到 HCC，并且发现严重脂肪变性和轻度结肠炎的小鼠 HCC 风险较高。目前，HCC 的预测非常困难。在某些情况下，严重的结肠炎会因食欲下降而逆转脂肪堆积。我们的研究结果清楚地表明，严重的脂肪性肝炎和轻度结肠炎同时是 NASH 和 IBD 患者发生 HCC 的必要条件。
